Mechanisms of and regulation of absorptive activity in the gallbladder will be investigated in the isolated rabbit gallbladder and in separated mucosa from the isolated rabbit gallbladder. Trans-mural absorptive activity will be measured in the standard in vitro chamber preparation, and the influence of various bile acids upon absorptive activity will be studied. In addition, the concentration of cyclic AMP and the activity of adenylate cyclase will be measured in mucosa isolated from rabbit gallbladders bathed in various bile acids and compared with appropriate controls. Bile acids are, of course, a normal constituent of the gallbladder contents, and some of the bile acids (particularly the dihydroxy bile acids) have been shown to effect transport via the cyclic AMP mechanism in the colon (analogous to the effect of cholera toxin on the small bowel). Thus it appears important to evaluate the effects of these compounds on the gallbladder in some detail. Studies will be continued on the mechanisms of biliary lipid excretion int he trained, unanesthetized dog equipped with Thomas cannula. The effects of different bile acids on the biliary excretion of lecithin and cholesterol will be studied. In particular, some unusual bile acids on the biliary excretion of lecithin and cholesterol will be studied. In particular, some unusual bile acids such as hyodeoxycholic acid (which has been shown to produce markedly elevated cholesterol concentrations in hamster bile) will be studied in the dog. By appropriate chromatographic methods and solvolysis the possible presence of significant quantities of bile acid sulphates will also be investigated during infusion with such bile acids as hyodeoxycholic acid. If such metabolites are found, this may provide an opportunity to investigate the effects of bile acid sulphages (if any) on biliary lipid excretion. These studies may ultimately have a direct bearing on the problem of cholelithiasis. Bibliographic references: Loeb, P.M., R.N. Berk, G.K. Feld and H.O. Wheeler. The biliary excretion of iodipamide. Gastroenterology 68: 554, 1975. Feld, G.K., P.M. Loeb, R.N. Berk and H.O. Wheeler. The choleretic effect of iodipamide. J. Clin. Invest. 55:528, 1975.